title: Pathogenesis of two axonopathies does not require axonal neurofilaments.
abstract: Neurofilaments are a major component of the axonal cytoskeleton and their abnormal accumulation is a prominent feature of the cytopathology encountered in several neurodegenerative diseases. Thus, an attractive and widely held model of pathogenesis involves the participation of disrupted neurofilaments as a common toxic intermediate. Here, in direct contrast to this hypothesis, we show that two neurodegenerative disease models in the mouse, dystonia musculorum (dt) and a superoxide dismutase 1 (SOD1)-mediated form of human motor neuron disease (amyotrophic lateral sclerosis, ALS), progress with little or no abatement on a transgenic background in which neurofilaments are withheld from the axonal compartment. By specifically excluding a necessary role for axonal neurofilaments, our observations redefine the components of the pathogenic pathway leading to axon disruption in these two degenerative diseases.
authors.affiliation: INSERM CJF 97-08 and University of Angers, CHU, France.
authors.forename: J
authors.initials: J
authors.lastname: Eyer
authors.forename: D W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
authors.forename: A C
authors.initials: AC
authors.lastname: Peterson
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D001369:Axons / Q000648:ultrastructure*; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D004422:Dystonia Musculorum Deformans / Q000209:etiology* / Q000473:pathology; D000071821:Dystonin; D005727:Ganglia, Spinal / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins / Q000235:genetics; D024041:Non-Fibrillar Collagens; D011993:Recombinant Fusion Proteins / Q000235:genetics; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D024041:Non-Fibrillar Collagens; D011993:Recombinant Fusion Proteins; D000097805:Collagen Type XVII; C486268:DST protein, human; C095667:Dst protein, mouse; C051774:neurofilament protein H